US4405606A - Method for arresting fulminating infection - Google Patents
Method for arresting fulminating infection Download PDFInfo
- Publication number
- US4405606A US4405606A US06/260,144 US26014481A US4405606A US 4405606 A US4405606 A US 4405606A US 26014481 A US26014481 A US 26014481A US 4405606 A US4405606 A US 4405606A
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- agent
- iron
- haptoglobin
- infection
- hemoglobin
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- Expired - Fee Related
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- 208000015181 infectious disease Diseases 0.000 title claims abstract description 22
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 68
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 43
- 102000014702 Haptoglobin Human genes 0.000 claims abstract description 37
- 108050005077 Haptoglobin Proteins 0.000 claims abstract description 37
- 229910052742 iron Inorganic materials 0.000 claims abstract description 34
- 210000001124 body fluid Anatomy 0.000 claims abstract description 16
- 239000010839 body fluid Substances 0.000 claims abstract description 16
- 241001465754 Metazoa Species 0.000 claims abstract description 12
- 238000009739 binding Methods 0.000 claims abstract description 8
- 238000001179 sorption measurement Methods 0.000 claims abstract description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 230000000536 complexating effect Effects 0.000 claims description 10
- 102000013271 Hemopexin Human genes 0.000 claims description 6
- 108010026027 Hemopexin Proteins 0.000 claims description 6
- 102000004338 Transferrin Human genes 0.000 claims description 6
- 108090000901 Transferrin Proteins 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 239000008174 sterile solution Substances 0.000 claims description 5
- 239000012581 transferrin Substances 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 3
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- 239000000463 material Substances 0.000 claims description 3
- 108010054147 Hemoglobins Proteins 0.000 abstract description 35
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/168—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
Definitions
- the present invention relates to a method for arresting the development of fulminating infection in traumatized animal tissue.
- a method of arresting fulminating infections of traumatized animal tissue comprises administering to such tissue at the site of trauma, an agent capable of binding the iron component of the body fluid that has been released by the traumatization of the tissue and thereby made available for adsorption by infection-promoting organisms.
- the agent is administered in an amount sufficient to bind all of the iron thus available, to render the iron unavailable to the infection-promoting organisms.
- the agent of the invention comprises at least one complex-forming protein that is administered in exogenous form, and preferably comprises the protein haptoglobin.
- the agent may comprise haptoglobin alone.
- the agent may include haptoglobin in combination with other binding proteins, such as transferrin or hemopexin, individually and in mixtures with each other.
- the agent of the present invention may be administered in intraperitoneal fashion in a sterile solution containing the agent in a concentration that may range from about 1.0 to about 100 mg./ml.
- Direct dosage administration may be utilized, as well as incorporation into conventional irrigation fluids utilized to treat body wounds.
- the complex binding proteins of the agent of the present invention are naturally occurring, and may be derived from human plasma, or may be synthetically prepared.
- the binding proteins are universally compatible with animal tissues and animal body fluids, and the risk of adverse reactions to their administration is non-existent.
- the present method of treatment is particularly useful in conjunction with current treatment methods employing antibiotic therapy.
- FIGS. 1 and 2 graphically represent the results of in vitro comparative testing of the method of the present invention.
- FIGS. 3 and 4 graphically represent the results of in vivo testing of the method of the present invention.
- a method for arresting fulminating infection of traumatized animal tissue comprises administering to such tissue an agent capable of binding iron made available to infection-promoting organisms by body fluid released by the traumatization of the tissue, so as to block the adsorption of the iron by the organisms.
- the agent is administered in an amount sufficient to bind all of the available iron, which amount is generally proportional to the quantity of released body fluid.
- the agent preferably comprises at least one complexing protein, and in the instance where the iron containing body fluid comprises the hemoglobin fraction of blood, the agent comprises the protein haptoglobin.
- the present invention is predicated upon experimental studies discussed earlier that investigated the relationship between bacterial growth and the presence of blood adjacent the locus of tissue trauma.
- the hemoglobin fraction of the blood provided a nutrient medium for bacteria that could not be duplicated by administration of other non-iron containing fractions of blood, such as albumin. It was thus concluded that the iron content of the blood fraction served to promote the accelerated growth of the bacteria that defies control by conventional therapeutic techniques.
- the bacterial organisms were capable of a form of digestion of the hemoglobin to abstract and thereby adsorb the contained iron; bacterial proteases performed proteolytic clevage of the hemoglobin fraction to abstract the iron component.
- the iron-containing fractions of the blood are maintained secure against such breakdown by association with certain complexing proteins.
- the fraction hemoglobin is secured by association with the protein haptoglobin, while the heme fraction is bound by the protein hemopexin, and iron occurring as iron salts is bound by the protein transferrin.
- Each of the foregoing binding or complexing proteins is present in relatively small amounts under normal circumstances. Increases of the levels of these proteins can occur gradually, in response to the onset of certain internal pathological conditions, however the body is not equipped to rapidly provide the relatively massive amounts of these proteins necessary to maintain iron in the unavailable sequestered state, in the instance where tissue trauma takes place and the blood is released from the vascular system into the peritoneum and thereby into contact with infection-promoting bacteria.
- red blood cells derived from one 1 milliliter of blood can yield up to 150 milligrams of hemoglobin after proteolytic breakdown, a value far exceeding the capacity of any haptoglobin normally present in that quantity of blood.
- the agent comprising the complexing protein is derived in exogenous form, and is preferably administered in a sterile solution.
- the quantity of agent may naturally vary, in relation to the nature and extent of body fluid liberated by the trauma.
- the proteins haptoglobin, hemopexin and transferrin exist in human blood in amounts of approximately 1.2 mg./ml.
- the quantities of such materials administered in accordance with the present method must naturally exceed these amounts substantially, and generally varies in relation to the amount of body fluid released by the trauma, in a ratio with respect thereto ranging up to about 3 to 1.
- the ratio of the amount of agent administered with respect to body fluid released may preferably range from about 2 to 1 to about 3 to 1.
- the agent is preferably utilized in conjunction with conventional antibiotic therapy, and provides the advantage of preventing the acceleration of bacterial growth that has rendered such therapy inadequate in the past.
- Bacterial growth generally occurs slowly during the initial 24 hours of innoculation, during which time growth is characterized by a lag phase. After this period is surpassed, accelerated or logarithmic growth commences, and full infection of the tissues become pronounced and severe. It is has been found that control of the spread of bacterial infection can be achieved if growth during this initial 24 hour period can be either restrained or reduced in rate.
- the agent of the present invention may be administered in a variety of ways; a sterile solution containing the agent may be directly administered by injection or otherwise to the locus of tissue trauma, or may be incorporated in an irrigation fluid utilized to wash body wound areas.
- the solutions containing the agent may be prepared to a concentration of up to about 100 milligrams per milliliter, and may preferably contain from about 1.0 to about 100 milligrams per milliliter of the agent.
- the foregoing quantities are illustrative only, as the quantity of agent present in the solutions may vary within the scope of the invention.
- the complexing or binding proteins useful in the agent of the present invention include those binding proteins that are naturally occurring in the body fluid, namely haptoglobin, hemopexin and transferrin.
- haptoglobin may be utilized alone in the agent, as the majority of tissue trauma results in the release of red blood cells which, after proteolytic breakdown by the enzymes of the bacteria, primarily yield hemoglobin.
- Haptoglobin is specific in its binding reaction with hemoglobin, and has been observed to form a complex with the hemoglobin that resists the proteolytic breakdown by the enzymes of the bacteria.
- the agent of the present invention may contain other complexing or binding proteins in addition to haptoglobin.
- Haptoglobin is specifically reactive with hemoglobin, however it is unable to bind other forms of iron, such as heme and iron existing in salt form or the like. Therefore, the present agent may include the proteins hemopexin and transferrin, either alone or in mixtures, in the instance where the additional forms of available iron may exist. For example, such non-bound additional sources of iron may exist in the instance of abdominal surgery, hemorraghic pancreatitis, bacterial peritonitis, and the like.
- the exact proportions of the respective proteins may vary, however, most instances will require haptoglobin as the primary or major component of the agent.
- the exact proportion of the respective forms of available iron could be determined by prompt analysis of a sample of the released blood, and the agent could be modified in composition accordingly.
- binding or complexing proteins of the agent of the present invention may be obtained by isolation from human plasma, or may be synthetically prepared by genetic transplant techniques presently known. The exact preparation of the binding proteins of the present invention is within the skill of the art and does not per se form a part of the present invention.
- Group 1- The bacteria E. coli alone.
- the data from the respective groupings is identified by the corresponding graphical symbol set forth in the legends accompanying each Figure.
- the data points plotted in FIG. 1 represent the respective mean and standard deviation values determined from a comparison of three samples of each grouping observed and counted at the indicated time interval.
- the rate of growth of the bacteria E. coli alone can be seen to be relatively flat, so that the initial or lag phase of bacterial growth is apparent.
- the addition of the hemoglobin to the growth medium alone results in a dramatic acceleration in bacterial growth.
- This growth is neutralized in the instance of Group 3, wherein a comparable quantity of haptoglobin is introduced together with the hemoglobin, and is similar in rate to the growth pattern of the bacteria inoculated with haptoglobin alone.
- the results of the Group 4 media illustrates the specificity of haptoglobin for hemoglobin.
- haptoglobin was introduced, however hemin, containing a variant form of available iron was provided in place of hemoglobin. Haptoglobin proved ineffective in this instance, and greatly accelerated growth of the bacteria was in evidence.
- Group 1- These rats were innoculated with 2 ⁇ 10 9 E. coli bacteria alone.
- the bacteria utilized in this test were isolated from a fatal human case of septicemia. After injection, the rats were placed under observation for a period of 72 hours, to note the adverse effect, if any, caused by the respective injections. The rats were regularly observed during this period, and the results regarding survival were gathered and are presented in graphical form in FIG. 3. The identity of the results of the respective groups may be determined from the legends accompanying the graph.
- results of this example illustrates that haptoglobin exerts a neutralizing affect upon hemoglobin in the presence of bacteria in an in vivo situation.
- Example 2 Additional in vivo testing was conducted with laboratory rats in a manner similar to that set forth in Example 2 above. Two batteries of tests were conducted, each battery differing only in the number of rats utilized, and the specific composition of the innocula.
- Group 1--Inoculum comprised 20 mg. stroma-free hemoglobin (SFHb) (3.4 g %), 2.5 ⁇ 10 7 E. coli bacteria and 66.7 mg. Albumin.
- Group 2--Inoculum comprised 2.5 ⁇ 10 7 E. coli and 86.7 mg. Albumin, alone.
- the second battery of tests were performed with three groups of eight rats each, the rats otherwise identical to those utilized in the first battery of testing.
- the inocula utilized in the second battery of tests are set forth below.
- Group 4--The Inoculum comprised 20 mg. stroma-free hemoglobin (SFHb) (3.4 g %), 2.5 ⁇ 10 7 E. coli bacteria and 66.7 mg. Albumin.
- Group 5--Inoculum comprised 2.5 ⁇ 10 7 E. coli and 86.6 mg. Albumin, alone.
- FIG. 4 graphically confirms the results set forth in Table II, above.
- the present method is particularly useful in conjunction with conventional antibiotic therapy to control and eliminate infections that arise adjacent traumatized animal tissue.
- the present method serves only to prevent the uncontrolled development of the infection, to permit the conventional therapy as well as the body defenses to develop an effective counter-attack to the spreading infection.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Inorganic Chemistry (AREA)
- Botany (AREA)
- Marine Sciences & Fisheries (AREA)
- Materials Engineering (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Absorbent Articles And Supports Therefor (AREA)
- Materials For Medical Uses (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
TABLE I ______________________________________ RAT MORTALITY AFTER 48 HOURS MORTALITY GROUP NO. No. Dead Total No. Tested ______________________________________ 1 6 7 2 1 7 3 0 7 4 6 8 5 0 8 6 0 8 ______________________________________
TABLE II ______________________________________ SUMMARY - TABLE I DATA MORTALITY INOCULUM No. Dead Total No. Tested ______________________________________ E. coli alone 1 15 E. coli plus 12 15 hemoglobin E. coli, hemoglobin 0 15 plus haptoglobin ______________________________________
Claims (8)
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/260,144 US4405606A (en) | 1981-05-04 | 1981-05-04 | Method for arresting fulminating infection |
EP82901777A EP0077826B1 (en) | 1981-05-04 | 1982-05-03 | Agents for arresting fulminating infection |
CA000402167A CA1197779A (en) | 1981-05-04 | 1982-05-03 | Method and agents for arresting fulminating infection |
JP57501766A JPS58500566A (en) | 1981-05-04 | 1982-05-03 | drugs used to prevent bacterial infections in animals |
PCT/US1982/000584 WO1982003770A1 (en) | 1981-05-04 | 1982-05-03 | Method and agents for arresting fulminating infection |
AU85250/82A AU555515B2 (en) | 1981-05-04 | 1982-05-03 | Method and agents for arresting fulminating infection |
AT82901777T ATE40293T1 (en) | 1981-05-04 | 1982-05-03 | AGENT FOR INHIBITING FULMINANT INFECTION. |
US06/374,580 US4462989A (en) | 1981-05-04 | 1982-05-03 | Method and agents for arresting infection |
DE8282901777T DE3279385D1 (en) | 1981-05-04 | 1982-05-03 | Agents for arresting fulminating infection |
ZA823057A ZA823057B (en) | 1981-05-04 | 1982-05-04 | Method and agents for arresting fulminating infection |
JP2062492A JPH03205058A (en) | 1981-05-04 | 1990-03-12 | Medical device used for inhibiting animal microbism |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/260,144 US4405606A (en) | 1981-05-04 | 1981-05-04 | Method for arresting fulminating infection |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/374,580 Continuation-In-Part US4462989A (en) | 1981-05-04 | 1982-05-03 | Method and agents for arresting infection |
Publications (1)
Publication Number | Publication Date |
---|---|
US4405606A true US4405606A (en) | 1983-09-20 |
Family
ID=22987948
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/260,144 Expired - Fee Related US4405606A (en) | 1981-05-04 | 1981-05-04 | Method for arresting fulminating infection |
Country Status (8)
Country | Link |
---|---|
US (1) | US4405606A (en) |
EP (1) | EP0077826B1 (en) |
JP (2) | JPS58500566A (en) |
AU (1) | AU555515B2 (en) |
CA (1) | CA1197779A (en) |
DE (1) | DE3279385D1 (en) |
WO (1) | WO1982003770A1 (en) |
ZA (1) | ZA823057B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997015313A1 (en) * | 1995-10-26 | 1997-05-01 | Baxter International Inc. | Therapeutic use of hemoglobin in promoting wound healing |
EP1013283A2 (en) * | 1992-04-02 | 2000-06-28 | Immuno Japan Inc. | Pharmaceutical and foodstuff compositions containing transferrins and antibacteral agents for potentiating host defence activity and the treatment of infections |
GB2393656A (en) * | 2002-10-01 | 2004-04-07 | Johnson & Johnson Medical Ltd | Wound dressing with controlled release of therapeutic agent |
US20050020672A1 (en) * | 1994-04-08 | 2005-01-27 | The Procter & Gamble Company | Methods of extending mammalian life span via iron chelating compounds that reduce free radical damage in mammals |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE460017B (en) * | 1984-03-14 | 1989-09-04 | Landstingens Inkopscentral | BACTERY-ADDRESSING COMPOSITION IN WATER-SOLUBLE FORM |
US4692462A (en) * | 1985-03-18 | 1987-09-08 | Menley & James Laboratories, Ltd. | Compositions and method of controlling transdermal penetration of topical and systemic agents |
DE4311546A1 (en) * | 1993-04-07 | 1995-01-19 | Emmanuel Dr Rer Nat Bisse | Use of colloidal silicon dioxide for the treatment of sickle cell anemia, malaria and exogenously induced leukopenias |
KR20020023208A (en) * | 2001-12-31 | 2002-03-28 | 박상율 | A method of discovery and treatment concerning a disease germ occuring a geriatric diseases |
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- 1982-05-03 WO PCT/US1982/000584 patent/WO1982003770A1/en active IP Right Grant
- 1982-05-03 EP EP82901777A patent/EP0077826B1/en not_active Expired
- 1982-05-03 CA CA000402167A patent/CA1197779A/en not_active Expired
- 1982-05-03 DE DE8282901777T patent/DE3279385D1/en not_active Expired
- 1982-05-03 JP JP57501766A patent/JPS58500566A/en active Granted
- 1982-05-04 ZA ZA823057A patent/ZA823057B/en unknown
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1990
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Cited By (8)
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EP1013283A2 (en) * | 1992-04-02 | 2000-06-28 | Immuno Japan Inc. | Pharmaceutical and foodstuff compositions containing transferrins and antibacteral agents for potentiating host defence activity and the treatment of infections |
EP1013282A2 (en) * | 1992-04-02 | 2000-06-28 | Immuno Japan Inc. | Pharmaceutical and foodstuff compositions containing transferrins and antibacteral agents for potentiating host defence activity and the treatment of infections |
EP1013283A3 (en) * | 1992-04-02 | 2002-08-07 | Immuno Japan Inc. | Pharmaceutical and foodstuff compositions containing transferrins and antibacteral agents for potentiating host defence activity and the treatment of infections |
EP1013282A3 (en) * | 1992-04-02 | 2002-08-07 | Immuno Japan Inc. | Pharmaceutical and foodstuff compositions containing transferrins and antibacteral agents for potentiating host defence activity and the treatment of infections |
US20050020672A1 (en) * | 1994-04-08 | 2005-01-27 | The Procter & Gamble Company | Methods of extending mammalian life span via iron chelating compounds that reduce free radical damage in mammals |
WO1997015313A1 (en) * | 1995-10-26 | 1997-05-01 | Baxter International Inc. | Therapeutic use of hemoglobin in promoting wound healing |
GB2393656A (en) * | 2002-10-01 | 2004-04-07 | Johnson & Johnson Medical Ltd | Wound dressing with controlled release of therapeutic agent |
GB2393656B (en) * | 2002-10-01 | 2005-11-16 | Johnson & Johnson Medical Ltd | Enzyme-sensitive therapeutic wound dressings |
Also Published As
Publication number | Publication date |
---|---|
DE3279385D1 (en) | 1989-03-02 |
WO1982003770A1 (en) | 1982-11-11 |
EP0077826A4 (en) | 1984-01-16 |
AU555515B2 (en) | 1986-09-25 |
JPH0251404B2 (en) | 1990-11-07 |
JPH0478309B2 (en) | 1992-12-10 |
JPS58500566A (en) | 1983-04-14 |
CA1197779A (en) | 1985-12-10 |
JPH03205058A (en) | 1991-09-06 |
EP0077826A1 (en) | 1983-05-04 |
EP0077826B1 (en) | 1989-01-25 |
AU8525082A (en) | 1982-11-24 |
ZA823057B (en) | 1983-03-30 |
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